Ameliorative effect of trimetazidine on cisplatin-induced hepatotoxicity in rats

2016 ◽  
Vol 94 (2) ◽  
pp. 225-230 ◽  
Author(s):  
Hayam Ateyya ◽  
Hala Yosef ◽  
Manar A. Nader
Keyword(s):  
Liver Damage ◽  
Antioxidant Defense System ◽  
Serum Levels ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Protective Effects ◽  
Bax Protein ◽  
Ameliorative Effect ◽  
Glutamyl Transferase ◽  
Per Oral

This study was designed to evaluate the protective effects of trimetazidine (TMZ) against cisplatin (CP) induced liver damage in rats. Animals were distributed among 4 groups as follows: control group; TMZ group (20 mg/kg body mass, per oral), which was treated for 10 days; CP group (6 mg/kg, by intraperitoneal injection), which received a single injection; and the CP + TMZ group (20 mg/kg, per oral), which received TMZ 4 days before and 6 days after CP injection. The extent of hepatic damage was studied by assessing biochemical parameters and histopathological evaluation of the extracted liver tissue. The results revealed that liver enzymes were markedly elevated after injection of CP, as evident from significant increases in the serum levels of alanine transaminase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GT), and lactate dehydrogenase (LDH), as well as marked changes to the liver architecture, with a significant decrease in serum levels of albumin. There were also marked changes to the antioxidant defense system, as indicated by significant decreases in total antioxidants and hepatic levels of reduced glutathione (GSH) and superoxide dismutase (SOD), together with a significant increase in lipid peroxidation. However, there was a significant increase in the activity of hepatic nuclear factor kappa B (NF-κB) as well as hepatic Bax protein expression. We conclude that TMZ protects against CP-induced liver damage through scavenging free radicals and anti-inflammatory and antiapoptotic effects, as well as through reducing NF-κB activation.

scholarly journals PROTECTIVE ROLE AND ANTIOXIDANT ACTIVITY OF AQUEOUS EXTRACT OF ROSMARINUS OFFICINALIS AGAINST TRICHLOROACETATE-INDUCED TOXICITY IN LIVER OF MALE RATS

2018 ◽  
Vol 11 (6) ◽  
pp. 420
Author(s):  
Medhat Mostafa Abozid ◽  
Hoda Ea Farid
Keyword(s):  
Aqueous Extract ◽  
Liver Damage ◽  
Protective Role ◽  
Rosmarinus Officinalis ◽  
Male Rats ◽  
Control Group ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Group I ◽  
Glutamyl Transferase

 Objective: The current study was designed to estimate the potential protective role of the aqueous extract of rosemary (AER) (Rosmarinus officinalis) against trichloroacetic acid (TCA)-created hepatotoxicity in male albino rats.Methods: Forty male albino rats were separated into four groups of ten: Group I served as control; Group II was given AER (200 mg/kg/day) by gavage; Group III received TCA at the dose 50 mg/kg/day, and Group V was treated with AER (200 mg/kg/day) and received TCA (50 mg/kg/day). The experiment was carried out for 2 months.Results: The toxicity of TCA for rats was revealed by an elevation in liver marker enzymes activities (gamma-glutamyl transferase [GGT], alkaline phosphatase [ALP], aspartate transaminase [AST], alanine aminotransferase [ALT]) and conjugated bilirubin (CB) level, and a decrease in albumin and total protein (TP) levels. The TCA administration also caused a significant increase in the activities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), and also malondialdehyde (MDA) level in liver tissues. These biochemical effects were accompanied by histological indicators of liver damage. Treatment with ARE recovered the liver damage instigated by TCA, as showed by perfection of liver enzyme markers (GGT, ALT, AST, ALP), CB, TP and albumin; as well as antioxidant parameters (CAT, SOD, GPx) and lipid peroxidation (MDA) and amelioration of histopathology changes in the liver tissues.Conclusion: It could be concluded that AER supplementation for 2 months in TCA-induced toxicity in rats benefited hepatic antioxidant status and improved liver injury and damage in male albino rats exposed to TCA.

scholarly journals Serum Levels of Glutamate-Pyruvate Transaminase, Glutamate-Oxaloacetate Transaminase and Gamma-Glutamyl Transferase in 1494 Patients with Various Genotypes for the Alpha-1 Antitrypsin Gene

2020 ◽  
Vol 9 (12) ◽  
pp. 3923
Author(s):  
José María Hernández Pérez ◽  
Ignacio Blanco ◽  
Agustín Jesús Sánchez Medina ◽  
Laura Díaz Hernández ◽  
José Antonio Pérez Pérez
Keyword(s):  
Liver Damage ◽  
Serum Levels ◽  
Gamma Glutamyl Transferase ◽  
Glutamate Oxaloacetate Transaminase ◽  
Glutamate Pyruvate Transaminase ◽  
Gamma Glutamyl ◽  
Glutamate Pyruvate ◽  
Alpha 1 Antitrypsin ◽  
Glutamyl Transferase ◽  
Normal Genotype

Background: Patients with liver disease associated with alpha-1 antitrypsin deficiency (AATD) are homozygous for the Z mutation, leading to chronic liver damage. Objective: To assess the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and gamma-glutamyl transpeptidase (GGT) in patients with different genotypes for the alpha-1 antitrypsin (AAT) gene. Methods: Patients (n = 1494) underwent genotyping of the SERPINA1 gene, together with a determination of AAT and GOT and GPT and GGT transaminase levels. Patients with a deficient allele (n = 476) and with a normal genotype were compared. Results: A statistically significant association was found between deficient genotypes and GOT (p < 0.0003), GPT (p < 0.002), and GGT (p < 0.006). Comparing GOT levels in patients with PI*Z deficient variant versus those with normal genotype, an odds ratio (OR) of 2.72 (CI: 1.5–4.87) (p < 0.0005) was obtained. This finding was replicated with the PI*Z allele and the GPT values (OR = 2.31; CI: 1.45–3.67; p < 0.0003). In addition, a statistically significant association was found between liver enzymes and AAT values. Conclusion: The PI*Z allele seemed to be a risk factor for the development of liver damage. AAT deficient genotypes were associated with GOT, GPT, and GGT altered values. Low AAT levels were associated with high GPT and GGT levels.

Sildenafil, a phosphodiesterase-5 inhibitor, offers protection against carbon tetrachloride-induced hepatotoxicity in rat

2018 ◽  
Vol 29 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Olorunfemi R. Molehin ◽  
Anne A. Adeyanju ◽  
Stephen A. Adefegha ◽  
Oluwasanmi O. Aina ◽  
Blessing A. Afolabi ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Selective Inhibition ◽  
Guanosine Monophosphate ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Protective Agent ◽  
Glutamyl Transferase ◽  
Phosphodiesterase 5

AbstractBackground:Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5′-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4).Methods:CCl4(0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats.Results:CCl4significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05).Conclusions:The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.

scholarly journals Association of severity of depression, paroxetine use and markers of liver damage with QT interval duration in patients with alcohol dependence

2020 ◽  
Vol 77 (7) ◽  
pp. 680-687
Author(s):  
Sanja Vukadinovic-Stojanovic ◽  
Zlatan Stojanovic
Keyword(s):  
Liver Damage ◽  
Qt Interval ◽  
Serum Levels ◽  
Interval Length ◽  
Gamma Glutamyl Transferase ◽  
Qtc Interval ◽  
Chronic Alcoholic ◽  
Number Of Patients ◽  
Severity Of Depression ◽  
Glutamyl Transferase

Background/Aim. Patients suffered from chronic alcoholic disease very often have depression and cardiomyopathy. Treatment with several antidepressants is associated with prolonged QT interval, ventricular arrhythmias and sudden death. The aim of this study was to investigate the relation between the severity of depression, serum levels of gamma-glutamyl transferase (GGT), as a marker of liver damage, and the possible influence of paroxetine use on duration of QT interval in patient who started treatment of chronic alcoholic dependence. Methods. The study included 147 male patients (older than 18 years of age) suffering from alcohol addiction, who were also diagnosed with depressive disorder on the basis of DSM-IV criterion and positive Hamilton Rating Scale for Depression (HRSD) at the beginning of hospitalization. Out of total number of patients, 49 were randomly selected to be treated with antidepressant paroxetine at a dose of 20 mg once daily during 20 days. The global QTc interval was automatically determined. Results. By applying the generalised linear model, the statistically significant positive correlation between the length of QTc interval and serum values of GGT, that is, intensity of alcoholism (p = 0.002) and values of the HRSD score, that is, intensity of depression (p = 0.021) was established in the sample of 147 depressed alcoholic patients before the application of paroxetine. In spite of the vulnerability of patients due to the heart damage and the liver dysfunction arising from alcohol consumption, as well as altered patients' drugs metabolism, no elongation of QTc interval resulting from the application of paroxetine was established. The length of QTc interval 20 days after paroxetine administration was 401.43 ms and before paroxetine administration it was 403.31 ms. The difference in QTc interval length (after and before paroxetine administration) was ?QTc = - 1.88 ms (p = 0.524). Conclusion. The results indicated that the severity of depression and GGT serum levels positively correlated with the length of QT interval. On the other hand, paroxetine after 20 days of usage did not prolong QT interval.

scholarly journals Hepatoprotective and Reno-protective Effects of Artichoke Leaf Extract and Rosemary Extract against Paracetamol Induced Toxicity in Albino Rats

2020 ◽  
pp. 67-81
Author(s):  
Eman Aly Sadeek Fadlalla ◽  
Sahar Mousa Galal
Keyword(s):  
Leaf Extract ◽  
Serum Levels ◽  
Negative Control ◽  
Rosemary Extract ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Protective Effects ◽  
Liver And Kidney ◽  
Glutamyl Transferase ◽  
Artichoke Leaf Extract

Background: Paracetamol overdose is a predominant cause of hepatotoxicity and nephrotoxicity in both humans and experimental animals. There is an emerging focus on plant products to find a highly effective and reliable drug for the prevention of paracetamol –induced toxicity. Objective: In this study, we investigated the Hepatoprotective and Reno-protective Effects of artichoke (Cynara scolymus L.) Leaf extract and rosemary (Rosmarinus officinalis L.) extract against paracetamol Induced toxicity in Albino Rats. Materials and Methods: Rats were divided into five groups: Negative control, paracetamol (1000 mg/kg dose) PCT, artichoke leaf extract “ALE” (1.5  g/kg, orally + paracetamol for 30 d), rosemary extract “RE” (125  mg/kg + paracetamol for 30 days) and the last group was treated with PCT+ ALE+ RE for 30 days. Results: Paracetamol caused marked liver damage as noted by significant increased activities of serum aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase. Paracetamol also raised serum levels of urea, creatinine, and Cystatin-C. In addition, there was a significant decrease in serum total protein and albumin. Paracetamol caused an elevation in lipid peroxidation paralleled with significant decline in reduced glutathione (GSH) level and activities of glutathione-S- transferase (GST), glutathione (GPX) peroxidase, and superoxide dismutase (SOD) in the liver and kidney. These results are confirmed in the histological examination of the liver and kidney. Conclusion: Treatment with artichoke leaf extract (ALE) and rosemary extract (RE) produced a potential protection of the liver and kidney against biochemical and histological alterations and oxidative stress induced by paracetamol.

scholarly journals Antioxidant and Hepatoprotective Effects of Methanolic Extracts of Zilla spinosa and Hammada elegans Against Carbon Tetrachlorideinduced Hepatotoxicity in Rats

2018 ◽  
Vol 16 (1) ◽  
pp. 133-140 ◽  
Author(s):  
Riaz Ullah ◽  
Mansour S. Alsaid ◽  
Abdelaaty A. Shahat ◽  
Almoqbil Abdulaziz Naser ◽  
Abdullah A. Al-Mishari ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Unmet Need ◽  
Serum Levels ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Methanolic Extracts ◽  
Group 5 ◽  
Group 2 ◽  
Glutamyl Transferase ◽  
Antioxidant Effects

AbstractThe detoxification, metabolism, and excretion of various endogenous and exogenous materials occur mainly in the liver. Liver diseases are a global concern, and classified as chronic hepatitis, cirrhosis, and hepatosis. The development of safe hepatoprotective agents remains an unmet need. Therefore, we investigated the antioxidant effects of methanolic and n-hexane fractions of Zilla spinosa (ZSM and ZSH, respectively) and Hammada elegans (HEM and HEH, respectively) against carbon tetrachloride (CCl4)-induced liver toxicity in rats. Antioxidant activity was studied by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The rats were divided into 11 groups (n=6)–group, 1 (control), group 2 (CCl4 only), group 3 (CCl4+silymarin 10 mg/kg), group 4 (CCl4+HEM 250 mg/kg), group 5 (CC14+HEM 500 mg/kg), group 6 (CCl4+HEH 250 mg/kg), group, 7 (CCl4+HEH 500 mg/kg), group, 8 (CCl4+ZSM 250 mg/kg), group 9 (CCl4+ZSM 500 mg/kg), group 10 (CCl4+ZSH 250 mg/kg), and group 11 (CCl4+ZSH 500 mg/kg). Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, and total bilirubin were measured. The extent of hepatic injury was histopathologically assessed. Treatment with ZSM and ZSH at 250 and 500 mg/kg did not significantly affect biochemical results compared with the CCl4 only group. However, treatment with both HEM and HEH at 250 and 500 mg/kg provided significant (p<0.001) results compared with the CCl4 only group. These results were consistent with histological findings. HEM and HEH at 250 μg/mL significantly inhibited DPPH radical formation by 38.E6 and 35.65%, rerpectively. However antioxidant effects of ZSM and ZSH were insignificant.

The ameliorative effect of Aspergillus awamori on aflatoxin B1-induced hepatic damage in rabbits

2017 ◽  
Vol 10 (4) ◽  
pp. 363-373 ◽  
Author(s):  
D.H. Abdelhady ◽  
M.A. El-Abasy ◽  
S.S.E. Abou-Asa ◽  
Z.I. Elbialy ◽  
M. Shukry ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Damage ◽  
Mononuclear Cells ◽  
Aspergillus Awamori ◽  
Phagocytic Index ◽  
Total Serum ◽  
Gamma Glutamyl Transferase ◽  
Hepatic Expression ◽  
Ameliorative Effect ◽  
Glutamyl Transferase

This study was conducted to investigate the effect of dietary supplementation of Aspergillus awamori on aflatoxin B1 (AFB1)-induced liver damage in rabbits. Administration of AFB1 (0.3 mg/kg diet) led to a significant reduction in body weight, body weight gain, total feed intake, total serum proteins, albumin, high density lipoprotein-cholesterol, phagocytic activity, phagocytic index, and the antioxidant enzyme, glutathione peroxidase (GPx). Moreover, AFB1 administration was associated with a significant increase in feed conversion ratio, lipid peroxidation and serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase and total bilirubin. In addition, livers of AFB1-supplemented animals showed fatty degeneration with vacuolisation, focal areas of necrosis, mononuclear cells infiltration hyperplasia of bile ducts and sinusoids. A significant increase in the hepatic expression of the biotransformation gene (Cyp3A6), stress-sensitive genes (HO1 and SOD1), and inflammation-related genes (IL6, TNFa, NF-kB, and Cox2) was also observed. Supplementation of the diets with 0.05, 0.1 or 0.15% A. awamori ameliorated all AFB1 deleterious effects with the best improvement observed at the lowest concentration. This is the first investigation to report that supplementation of rabbit diets with A. awamori has an ameliorative effect against AFB1-induced liver damage possibly through preventing hepatic oxidative stress, promoting the antioxidant defence systems, and inhibiting expression of Cyp3A6, HO1, SOD1, IL6, TNFa, NF-kB, and Cox2. Therefore, A. awamori could be used as a potential preventive or therapeutic agent for aflatoxicosis.

scholarly journals TIME COURSE STUDY OF COMBINED N-ACETYL-P-AMINOPHENOL AND DICLOPHENAC INDUCED-HEPATOTOXICITY AND OXIDATIVE STRESS IN WISTAR RATS

2021 ◽  
Vol 46 (2) ◽  
Author(s):  
O. A Dosumu ◽  
D. I. Akinloye ◽  
O. B. Onunkwor ◽  
F. C. Thomas ◽  
R. A. Adeyemo
Keyword(s):  
Oxidative Stress ◽  
Liver Damage ◽  
Wistar Rats ◽  
Time Course ◽  
Time Dependent ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Dependent Manner ◽  
Glutamyl Transferase ◽  
And Oxidative Stress

The abuse of combined acetaminophen or N-acetyl-p-aminophenol (APAP) and diclofenac (DIC) due to their analgesics, anti-inflammatory and antipyretic properties is a predominant cause of hepatotoxicity and oxidative stress. This study investigated the time-course effects of APAP, DIC and their combination on biomarkers of hepatic function and oxidative stress in rats. Forty male Wistar rats were randomly divided into four groups of 10 animals each as follows; control (distilled water), APAP only, DIC only and APAP + DIC for 4 weeks. Indices of liver damage (serum ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase and bilirubin) were measured. Oxidative stress biomarkers (MDA, malondialdehyde; NO, nitric oxide; CAT, Catalase activity; SOD, superoxide dismutase activity; GSH content, reduced glutathione), GR, glutathione reductase, and GST, glutathione-S-transferase) were also determined using spectrophotometric methods. Statistical analysis was done using one-way ANOVA with p < 0.05 considered significant. Acetaminophen and diclofenac caused marked liver damage as noted by time-dependent significant (p < 0.05) increased activities of serum ALT, AST, ALP, GGT, and bilirubin levels as well as significant (p < 0.05) increase in hepatic MDA and NO levels as compared to the control group. Hepatic GSH content, SOD, CAT, GPx, GST and GR activities were decreased significantly (p < 0.05) in all acetaminophen and diclofenac-treated groups compared to normal control in a time-dependent manner. These findings suggest that prolonged administration of diclofenac, acetaminophen or their combination may induce hepatotoxicity, oxidative stress and alteration of hepatic antioxidant status in a time-dependent manner.

Withdrawn: Hepatoprotective effects of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) hydro-alcholic extract on non-alcoholic fatty liver-induced rats

2016 ◽  
Vol 3 (5) ◽  
pp. 143
Author(s):  
Fatemeh Almasi ◽  
Mozafar Khazaei ◽  
Shima Chehrei ◽  
Ali Ghanbari
Keyword(s):  
Fatty Liver ◽  
Liver Tissue ◽  
Serum Lipid ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Lipid Profiles ◽  
Control Group ◽  
Tribulus Terrestris ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver induces many complications to the liver tissue and also serum related parameters. Medicinal plants are the safe therapeutic strategy for the treatment of diseases. In this regards, the present study was conducted to evaluate the effect of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) extract on non-alcoholic fatty liver in rats. In this experimental study, thirty male Wistar rats were divided into five groups (n = 6). Animals in experimental groups were received high fructose diet (70%) (HDF) daily alone or in combined with daily intraperitoneal injection of 500, 700 and 1,000 mg/kg extract of T. terrestris. Control group of rats was feed with standard chow. The serum levels of biomarkers of liver and serum lipid profiles were assessed, also histopathological examination of liver tissue done. Data were analyzed using One-way ANOVA method followed by Tukey’s post-hoc multiple comparison test and P < 0.05 was considered statistically significant. There were significant improvements for biomarkers of liver tissue (P < 0.05) and serum lipid profiles (P < 0.01) in the HFD-fed rats that were treated with T. terrestris extract compare to HFD-fed group. In addition, accumulation of lipids in hepatocytes was significantly reduced in the HFD-fed + extract administrated groups in comparison to HFD-fed rats (P < 0.01). T. terrestris extract has protective effects against non-alcoholic fatty liver by changing biomarkers of liver tissue, serum lipid profiles and histopathological anomalies of liver tissue, to normal range.

scholarly journals Assessment of the Level of GABA and Some Trace Elements in Blood in Children who Suffer from Familial Febrile Convulsions

2014 ◽  
Vol 2 (1) ◽  
pp. 68-73 ◽  
Author(s):  
Osama N. Salah ◽  
Ehab R. Abdelraouf ◽  
Marwa H. Abdelhameed ◽  
Ahmed A. Dawood ◽  
Adel F. Hashish ◽  
...  
Keyword(s):  
Febrile Seizure ◽  
Serum Magnesium ◽  
Serum Zinc ◽  
Febrile Convulsion ◽  
Serum Levels ◽  
Serum Copper ◽  
Control Group ◽  
Protective Effects ◽  
Gamma Aminobutyric Acid ◽  
Electrolyte Disturbances

Febrile seizure is one of the most common neurological problems during childhood. The etiology and pathogenesis of febrile seizure remain unknown. However, several factors such as vitamin B6 deficiency, electrolyte disturbances, and reduction in serum zinc, selenium, magnesium levels, and low gamma - aminobutyric acid (GABA) levels are thought to play a role in the pathogenesis of febrile seizure. The present study included twenty children from 10 families, 11 were male and 9 were female. Each family has at least 2 members with a history of febrile convulsion. All cases were subjected to the following: Determination of serum levels of copper, zinc, magnesium, selenium level in serum, and plasma level of γ-aminobytaric acid (GABA). Serum levels of selenium and GABA were statistically significantly low in comparison with controls. Serum copper was statistically significantly higher in cases than controls, while serum zinc showed no significant changes in the cases of febrile convulsion compared with the control group. The mean Zn level in the serum of febrile convulsion was found to be at lower level than in the control group. The serum magnesium was significantly low in cases than controls. The logistic regression model in our study shows that Selenium and Magnesium have protective effects, while Copper has causative effect.

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